APPLICANT'S DESCRIPTION: This project proposes development of a new tool for the research and potentially the treatment of chronic pain. In Phase I, a potent and specific conjugate between substance P and the ribosome- inactivating protein saponin was produced. In Phase II, this reagent will be optimized by making it homogeneous, more specific, more active and easier for the customer to use. The newly optimized reagent will be compared to the reagent used in Phase I for ability to eliminate NK-1 receptor-bearing neurons, in the dorsal horn of the spinal cord. Data gathered with the new construct may indicate that the substance P toxin is therapeutically useful in pain management. The success of SP-SAP in vivo has indicated that other peptide-toxins can be commercialized. In order to more fully address questions about pain transmission, it is proposed to produce a conjugate between dermorphin, a mu opioid receptor-specific agonist, and saponin in order to further delineate the pathway of pain transmission. This conjugate will also interest a broad group of researchers. PROPOSED COMMERCIAL APPLICATION: A small but enthusiastic market exists for these products as tools for basic researchers in the neuroscience community. The applicant provides a detailed estimate of cost and market size. The applicant organization currently markets a saponin conjugate for ablation of acetylcholine containing cells. There are currently no competing products. Thus, the applicant organization appears well poised to exploit the product. There is good reason to believe that the Phase II experiments will provide a foundation for more efficient production of additional targeted toxins that will add to the company's product line.